PARP while you can.
Top Line: PARP inhibitors are a good treatment for BRCA mutant breast cancers, so how do they do with triple-negative breast cancers (TNBC) at large?
The Study: TNBC exhibits a BRCAness molecular phenotype characterized by defects in DNA repair. Because BRCA mutated tumors are sensitive to both platinum agents and PARPi, these agents are garnering some serious attention in TNBC. The BrighTNness trial enrolled 634 women with stage II-III TNBC, 15% with germline BRCA mutations. They were randomized 1:1:2 to one of 3 neoadjuvant chemo regimens: paclitaxel→ doxorubicin/cyclophosphamide (T→AC) alone [1] versus carboplatin/T → AC [2] versus T/carbo/veliparib (a PARPi) → AC [3]. Remember, back in 2016, the carbo/veliparib combo was one of the big winners of the ISPY2 trial by almost doubling pathologic complete response (pCR) rate from 26% to 51%. BrighTNess confirms an advantage in pCR rate with carbo/veliparib/T → AC (53%) when compared to T→AC (31%). But--and this is a big BUT--the highest pCR rate was achieved with carbo/T → AC (58%) without any veliparib. In fact, no subset seemed to benefit from the addition of veliparib. But carbo doesn't come without a cost, namely febrile neutropenia in this trial. Oh, and don’t forget the xeloda for those who still don’t achieve a pCR.
Bottom Line: Adding carboplatin to neoadjuvant T→ AC chemotherapy for TNBC nearly doubles the pCR rate, while the PARPi veliparib doesn’t seem to provide any additional benefit.
The Study: TNBC exhibits a BRCAness molecular phenotype characterized by defects in DNA repair. Because BRCA mutated tumors are sensitive to both platinum agents and PARPi, these agents are garnering some serious attention in TNBC. The BrighTNness trial enrolled 634 women with stage II-III TNBC, 15% with germline BRCA mutations. They were randomized 1:1:2 to one of 3 neoadjuvant chemo regimens: paclitaxel→ doxorubicin/cyclophosphamide (T→AC) alone [1] versus carboplatin/T → AC [2] versus T/carbo/veliparib (a PARPi) → AC [3]. Remember, back in 2016, the carbo/veliparib combo was one of the big winners of the ISPY2 trial by almost doubling pathologic complete response (pCR) rate from 26% to 51%. BrighTNess confirms an advantage in pCR rate with carbo/veliparib/T → AC (53%) when compared to T→AC (31%). But--and this is a big BUT--the highest pCR rate was achieved with carbo/T → AC (58%) without any veliparib. In fact, no subset seemed to benefit from the addition of veliparib. But carbo doesn't come without a cost, namely febrile neutropenia in this trial. Oh, and don’t forget the xeloda for those who still don’t achieve a pCR.
Bottom Line: Adding carboplatin to neoadjuvant T→ AC chemotherapy for TNBC nearly doubles the pCR rate, while the PARPi veliparib doesn’t seem to provide any additional benefit.
From NCCN 2.2019: "Even though the results of randomized trials show improvement in pCR rates when carboplatin is added to anthracycline- and taxane-based chemotherapy, the long-term outcomes such as OS or DFS associated with the incorporation with carboplatin are not yet known. Therefore, at this time, the NCCN panel does not recommend the addition of carboplatin to neoadjuvant standard chemotherapy for patients with triple-negative breast cancer outside a clinical trial setting"
ReplyDeleteI wonder if they're going to change this to a preferred regimen for TNBC sometime soon.